The balance between excitation and inhibition is critical to cortical circuit function, and thus to the formation of representations in the brain. Furthermore, imbalances have been discovered in neurological disorders ranging from epilepsy to autism and schizophrenia. Cortical inhibitory interneurons are a diverse class of many distinct cell types, which differ in their anatomical targeting of the post-synaptic neuron, in their morphologies, and in their molecular signatures. The primary visual cortex (V1) is an excellent model system for studying how cortical circuits process information, because simple visual stimuli can be used to describe the selective response properties of each cell. Orientation tuning is an important property of cells in V1, but we still do not know how this selectivity arises. One theory is that intracortical connections, provided by recurrent excitatory connections between cells with similar properties and inhibitory interactions, which suppress responses to all orientations, are critical for refining this selectivity. I plan to study how two types of inhibition, soma-targeting and dendritic targeting, are involved in the formation and maintenance of visual representations in the primary visual cortex of the mouse. I will use newly available genetic approaches to specifically label three subtypes of inhibitory cells, soma-targeting parvalbumin-positive (PV+), dendrite-targeting calretinin-positive (CR+), and dendrite-targeting somatostatin- positive cells (SOM+). I expect that these two types of inhibition will demonstrate unique orientation properties, that soma-targeting PV+ cells will have sharp tuning, which would allow them to provide highly specified feedforward inhibition, and that the dendrite targeting CR+ and SOM+ cells will have broad or flat tuning, allowing them to enhance the contrast-independence of orientation tuning. In the final phase of this project, I will explore the plasticity of these specific subtypes of cells, with the hypothesis that PV+ cells will demonstrate higher levels of short-term plasticity than the other two cells types. PUBLIC HEALTH RELEVANCE: This project will increase our understanding of how specific aspects of the balance between excitation and inhibition contribute to the ability of brain circuits to accurately process information, and how these circuits adapt to change in the environment. This is critical to our understanding of brain function under normal conditions, and will improve the ability of clinical researchers to assess abnormalities in cortical circuit function that result from disease processes, such as autism, schizophrenia, and epilepsy.